title: Phase II study of topotecan and bevacizumab in advanced, refractory non--small-cell lung cancer.
abstract: BACKGROUND
  This clinical trial evaluated whether topotecan in combination with bevacizumab improved progression-free survival (PFS) in patients with advanced, refractory non--small-cell lung cancer in a second-line setting.
  
  
  METHODS
  Patients aged 18 years old and older received topotecan (4.0 mg/m(2)) on days 1, 8, and 15, and bevacizumab (10 mg/kg) on days 1 and 15 as intravenous infusions on a 28-day treatment cycle. Available tumor specimens were analyzed for ISG15 gene expression as a biomarker of response to topotecan.
  
  
  RESULTS
  Forty-two patients were enrolled in the study, with a median age of 62.5 years and a median of 3 (range, 1-7) prior treatment regimens. Almost half (n = 18, 42.9%) of the patients received prior bevacizumab therapy. PFS was 5.1 months (95% CI, 3.7-7.8 months), and overall survival was 11.5 months (95% CI, 6.8-15.5 months). Response rates were as follows: 14.3% partial response, 54.8% stable disease, and 28.6% progressive disease. Hematologic toxicities included grade 3 thrombocytopenia (n = 7, 16.7%), neutropenia (n = 4, 9.5%), and anemia (n = 2, 4.8%). One toxic death occurred due to pulmonary hemorrhage, and one patient experienced a grade 4 pulmonary embolism. Grade 3 nonhematologic adverse events were uncommon (< 8%). There was a trend for improved median PFS, 3.5 months vs. 1.8 months (P = .26), in patients with high ISG15 expression.
  
  
  CONCLUSIONS
  Bevacizumab in combination with topotecan as a salvage therapy for metastatic non--small-cell lung cancer is well tolerated and is worthy of further investigation.
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Powell
authors.forename: Amer
authors.initials: A
authors.lastname: Beitinjaneh
authors.forename: Mathewos
authors.initials: M
authors.lastname: Tessema
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bliss
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: Joseph
authors.initials: J
authors.lastname: Leach
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D019772:Topotecan
keywords: Bevacizumab; ISG15 expression; Non-small-cell lung cancer; Refractory; Second-line therapy; Topotecan